This application proposes a cross-disciplinary Center of Cancer Nanotechnology Excellence (CCNE) at Emory University and Georgia Tech that will integrate nanotechnology with cancer biomolecular signatures (biomarkers) for personalized and predictive oncology. The overarching scientific focus is to accelerate the development of bioconjugated nanoparticles for cancer molecular imaging, molecular profiling, and personalized therapy. The proposed research will further develop new nanoparticle reagents for co-targeting signal transduction pathways and its microenvironments that are involved in bone metastasis. This research is broadly applicable to many types of malignant tumors such as lung cancer, colorectal carcinoma, ovarian cancer, brain tumors, and lymphomas; but proof of concept research is focused on human prostate and breast cancers and their clinically aggressive phenotypes - including interrogations of cancer cells and patient tissue biopsies. A compelling reason for this focus is that breast and prostate cancers represent a number of compelling challenges and opportunities in human oncology such as high incidence and mortality, evidence that targeted therapies can improve survival in these cancers, and our linkages to NCI Specialized Programs of Research Excellence (SPORE) in both prostate and breast cancers. The CCNE has 6 "synergistic projects" with crossdisciplinary teams, each with expertise in nanotechnology, bioengineering, clinical oncology, and basic cancer biology. Project #1 will develop quantum dots and targeted nanoparticles for cancer molecular imaging (Nie). Project #2 will develop novel molecular beacons and activatable nanoprobes for gene expression studies of single cancer cells (Bao). Project #3 will optimize and translate "nanotyping" multicolor sets of antibody linked quantum dots to multiplex cancer biomarkers that can predict clinical outcomes and susceptibility to signal transduction inhibitors in medical oncology (Simons/O'Regan). Project #4 will develop surface-enhanced Raman spectroscopic (SERS) nanotags and atomic nanoclusters for molecular profiling in cancer pathology (Natan/Young). Project #5 will develop nanoparticle anti-cancer therapeutics using a new class of self-assembled and biodegradable nanoparticles (Shin). Project #6 will focus on basic cancer metastasis biology and creation of new reagents via bioconjugated nanoparticles to target metastatic cancer cell clones and their bone stromal microenvironments (Chung). These projects are supported by 5 core functions: nanomaterials synthesis and fabrication (Core 1 - Z. Wang); biocomputing and bioinformatics (Core 2 - M. Wang); tissue specimens and animal tumor models (Core 3 - Datta); onconanotechnology education and outreach (Core 4 - Simons); and center administration, biostatistics support, technology assessment, and commercialization (Core 5 - Nie/Simons/Murdock). This CCNE is strengthened by collaborations with three NCI CCCs, investment from the Georgia Research Alliance, Georgia Cancer Coalition, and industrial partners. The CCNE is embedded in the Winship Cancer Institute, a new integrated 280K sq ft cancer research and care building, and has a special constellation of US partners, the American Cancer Society and the Centers for Disease Control, for accelerating the discovery and clinical translation of nanotechnology to reducing the burden of human cancer.